Jinan University Institute of Tumor Pharmacology, College of Pharmacy, Jinan University, Guangzhou, Guangdong 510632, P.R. China.
Mol Med Rep. 2017 Dec;16(6):9217-9223. doi: 10.3892/mmr.2017.7685. Epub 2017 Oct 2.
Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder characterized by a chromosome translocation that generates the BCR‑ABL oncogene, which encodes a constitutively activated tyrosine kinase. Despite progress in controlling CML at the chronic phase by first and second generations of BCR‑ABL tyrosine kinase inhibitors (TKIs), effective drugs with good safety are not available for CML patients harboring T315I BCR‑ABL and those in advanced stages of CML. Therefore, there is an urgent requirement for the development of effective therapies against T315I BCR‑ABL. In the present study, it was demonstrated that pyrvinium pamoate, an anthelmintic drug approved by the Food and Drug Administration had potent inhibitory effects on growth and survival in CML cells with T315I BCR‑ABL. In addition, this agent was equally effective in inhibiting the Wnt/β‑catenin signaling in wild‑type and T315I BCR‑ABL CML cells. Thus, the clinical efficacy of pyrvinium pamoate in treating patients with CML bearing T315I BCR‑ABL should be further investigated.
慢性髓性白血病（CML）是一种克隆性骨髓增生性疾病，其特征在于染色体易位，产生 BCR-ABL 癌基因，该基因编码一种组成性激活的酪氨酸激酶。尽管第一代和第二代 BCR-ABL 酪氨酸激酶抑制剂（TKI）在控制 CML 的慢性期方面取得了进展，但对于携带 T315I BCR-ABL 的 CML 患者和 CML 晚期患者，仍然缺乏有效且安全性良好的药物。因此，迫切需要开发针对 T315I BCR-ABL 的有效治疗方法。在本研究中，证明了已被美国食品和药物管理局批准的驱虫药匹鲁卡品对携带 T315I BCR-ABL 的 CML 细胞的生长和存活具有很强的抑制作用。此外，该药物在抑制野生型和 T315I BCR-ABL CML 细胞中的 Wnt/β-连环蛋白信号通路方面同样有效。因此，应该进一步研究匹鲁卡品在治疗携带 T315I BCR-ABL 的 CML 患者中的临床疗效。
